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Cytokines TNFα, IFNγ and IL-2 Are Responsible for Signal Transmission from the Innate Immunity Protein Tag7 (PGLYRP1) to Cytotoxic Effector Lymphocytes

Laboratory of Molecular Immunogenetics of Cancer, Institute of Gene Biology RAS, Vavilova 34/5, 111394 Moscow, Russia
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Cells 2020, 9(12), 2602; https://doi.org/10.3390/cells9122602
Received: 3 November 2020 / Revised: 26 November 2020 / Accepted: 2 December 2020 / Published: 4 December 2020
(This article belongs to the Section Cellular Immunology)
Studies on the mechanisms of activation of cytotoxic lymphocyte subpopulations are an important research direction in modern immunology. This study provides a detailed analysis of the effect of Tag7 (PGRP-S, PGLYRP1) on the development of lymphocyte subpopulations cytotoxic against MHC-negative tumor cells in a pool of peripheral blood mononuclear cells (PBMCs). The results show that Tag7 can bind to the TREM-1 receptor on the surfaces of monocytes, thereby triggering the expression of mRNA TNFα and IFNγ. The appearance of these cytokines in conditioned medium leads to IL-2 cytokine secretion by CD3+CD4+ lymphocytes. In turn, IL-2 facilitates unspecific activation of three cytotoxic cell subpopulations in the PBMC pool: NK (CD16+CD56+), CD3+CD4+ and CD3+CD8+. These subpopulations appear after a certain period of incubation with Tag7 and show toxicity against tumor cells. View Full-Text
Keywords: PGLYRP1; cancer immunology; monocytes; TREM-1; cytokines; programmed cell death PGLYRP1; cancer immunology; monocytes; TREM-1; cytokines; programmed cell death
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    Doi: 10.5281/zenodo.4292193
    Link: https://zenodo.org/record/4292193#.X7-wD9UzbIU
    Description: Supplementary Fig. S1. Changes in cytotoxic activity of different lymphocyte subpopulations induced in PBMC incubated with Tag7 (10–9M) for different periods of time. Lymphocyte subpopulations were isolated by magnetic cell separation and tested for cytotoxicity against K562 cells. Data are presented as the mean ± SD of 3 independent experiments. Differences from the control in all cases are significant at * p < 0.03, ** p < 0.05 (Student t test). Supplementary Fig. S2. Secretion of IL-2 by CD3+CD4+ - lymphocytes incubated with TNFα or IFNγ for 24 and 48 hours. CD3+CD4+ - lymphocytes were isolated by magnetic cell separation from PBMC on 0 day and treated with TNFα or IFNγ. Conditioned medium from untreated lymphocytes was used as a control. The medium was sampled every 24 h to determine IL-2 level by ELISA. Data are presented as the mean ± SD of 3 independent experiments. Differences from the control in all cases are significant at * p < 0.05 (2-way ANOVA). Supplementary Fig. S3. Cytotoxicity Tag7-PBMC in presense specific antibodies to TNFα, IFNγ, IL-2. Each antibody (1:1000) was added to PBMC before 1h to Tag7 (10-9M). After 6 days of incubation PBMC were tested for cytotoxicity against K562 cells. Data are presented as the mean ± SD of 3 independent experiments. Differences from the control in all cases are significant at * p < 0.05 (Student t test).
MDPI and ACS Style

Sharapova, T.N.; Romanova, E.A.; Ivanova, O.K.; Sashchenko, L.P.; Yashin, D.V. Cytokines TNFα, IFNγ and IL-2 Are Responsible for Signal Transmission from the Innate Immunity Protein Tag7 (PGLYRP1) to Cytotoxic Effector Lymphocytes. Cells 2020, 9, 2602. https://doi.org/10.3390/cells9122602

AMA Style

Sharapova TN, Romanova EA, Ivanova OK, Sashchenko LP, Yashin DV. Cytokines TNFα, IFNγ and IL-2 Are Responsible for Signal Transmission from the Innate Immunity Protein Tag7 (PGLYRP1) to Cytotoxic Effector Lymphocytes. Cells. 2020; 9(12):2602. https://doi.org/10.3390/cells9122602

Chicago/Turabian Style

Sharapova, Tatiana N.; Romanova, Elena A.; Ivanova, Olga K.; Sashchenko, Lidia P.; Yashin, Denis V. 2020. "Cytokines TNFα, IFNγ and IL-2 Are Responsible for Signal Transmission from the Innate Immunity Protein Tag7 (PGLYRP1) to Cytotoxic Effector Lymphocytes" Cells 9, no. 12: 2602. https://doi.org/10.3390/cells9122602

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